Recent progress has been made in understanding mechanisms and consequences of injury to the CNS, and in augmenting CNS plasticity and regeneration after experimental spinal cord injury (SCI) in non-primates. The relevance of this work to injured primate systems remains to be established. Differences in neural anatomy and function, and inter-species differences in immune and inflammatory responses to injury, raise questions regarding the simple translation of findings from rodents to primates. In the last 4 years, our consortium has established a reliable and practical model of SCI in primates, and has tested potential treatments in this model. We have found both similarities and differences in the anatomy and functional properties of intact and lesioned rodent and primate spinal cords. Further, we have preliminary evidence that plasticity can be augmented after primate SCI, leading to improved functional outcomes. The renewal of this program will build upon these findings, aiming to contribute both mechanistic and empirical knowledge leading to the development of therapeutic strategies for promoting recoveryfrom primate SCI. This project brings together research groups in a collaborative effort to advance the understanding and treatment of SCI in the following aims over the next 5years: Specific Aim 1: Determine Mechanisms Underlying Spontaneous RecoveryAfter Acute C5-6 Hemisection Lesions in Primates: Anatomical, Electrophysiological and Functional Studies. Specific Aim 2: Determine Whether BDNF Delivery Into and Below a C5-6 Hemisection Lesion Will Promote Axonal Sprouting or Regeneration, and Functional Recovery. Specific Aim 3: Determine Whether BDNF Delivery Into and Below a C5-6 Hemisection Lesion, + cAMP Augmentation, Will PromoteAxonal Sprouting or Regeneration, and FunctionalRecovery.